The present invention refers to the use of N-acetylglucosamine for the therapy of degenerative diseases of the joints and of the connective and the supporting tissues as well as for the therapy of related diseases. Moreover, the invention comprises the use of N-acetylglucosamine for the production of drugs for corresponding therapies.
Degenerative diseases of the joints (arthrosis) are widespread with human beings as well as with animals of middle and higher age. They are a frequent reason for poor general condition and limited ability to work. One main reason for these diseases is the destruction of glucosaminoglycanes (GAG) which are an essential component of the cartilage substances and of other flexible elements as well as a contributor to the lubrication of the joints.
The therapy of these painful, partly inflammatory conditions often only takes place symptomatically with the aid of non-steroidal anti-inflammatory drugs such as, for instance, indomethacin, or even corticoids. Both groups of therapeuticals cause severe side effects and should therefore be used as little as possible. Moreover, the application of non-steroidal anti-inflammatory drugs and corticoids entails the danger of further shifting the metabolism of the GAGs in the direction of accelerated degradation. Thus, the advantages of momentary relief of the symptoms of the disease, such as pain and immobility of the joints, is--besides other risks--connected with the danger of an acceleration in the degenerative processes which cause the underlying disease.
It is well-knwon that in contrast to the above, glucosaminoglycanes or a precursor of GAGs, glucosamine, exert a causal therapeutical effect. That effect is, on the one hand, based upon the incorporation of the corresponding elements in to the GAGs and, on the other hand, on the stimulation of the new synthesis of GAGs caused by an increase in the concentration of precursors of their synthesis. An inhibition of the enzymatic decomposition processes is also assumed. Thus, there exists the possibility to favorably influence the metabolic processes being causal for the disease, and to thereby contribute to the healing or at least to the retardation of the degenerative processes being the origin of the disease.
Drugs available for the last-mentioned causal therapy, however, are also not yet ideal. GAGs, being isolated from biological material, have the disadvantage of being complex natural products: It is hardly possible, or at least extremely difficult, to define them clearly and their parenteral application is necessary for guaranteeing a sufficient bio-availability. Moreover, there always exists the risk of anaphylactical reactions. The limited solubility and the high viscosity of concentrated solutions make it even more difficult to administer them with the desired high dosage.
Instead of the natural GAGs, glucosamine sulfate has also been administered orally, intramuscularly and intraarticularly with good therapeutical effect. Glucosamine sulfate has the great advantage of being a clearly definable compound with respect to identity, purity and stability. Glucosamine sulfate, as a low-molecular natural substance, does not cause any allergies and hardly gives reason to expect toxic effects in case of the necessary dosage. On the other hand, glucosamine sulfate has an essential disadvantage, as can for instance be taken from the prescribing information Dona.RTM.200-S of Opfermann-Arzneimittel, 5060 Bergisch-Gladbach.
The oral form of glucosamine is obviously much less effective than the intravenous or intramuscular injection. A weekly oral dosage of 5,250 mg is recommended, while, parenterally, only 1,200 mg are necessary. The physiological pH-value of the more efficient injection preparation, however, is not sufficiently stable in solution. Thus, it is prepared, stored and delivered with an acidic pH-value, and has to be neutralized by the physician before use. For this purpose, a buffer is added to the glucosamine sulfate solution. Glucosamine sulfate solution and buffer as a whole have, in case of the necessary dosage and concentration, such a high osmolality relative to the blood that lidocaine has to be added as a local anaesthetic. Only by means of that additive can the pain caused by the injection into the joints by sufficiently reduced. Thus, the glucosamine sulfate, although not toxic as such, is combined with the side effects of the lidocaine (ECG and other circlatory disturbances, vertigo, vomiting).
Other preparations, as described in the recently published application EP 85 112 913.0, comprise complex mixtures of individual components showing quite a number of obvious disadvantages:
(a) The chemical stability of every element in the mixture is difficult to obtain, particularly under long-term storage conditions.
(b) The Health Authorities of many countries, for good reasons, behave very restrictively as far as the approval of combined preparations is concerned. Thus, evidence is required that every component is effective, and often in addition that the fixed combination of the individual components has specific advantages. Both types of evidence can hardly be given for combinations comprising more than two ingredients.
It is therefore an object of the present invention to overcome the above-mentioned disadvantages and to make available an agent with only one active principle for use in the therapy of degenerative diseases of the joints and of the connective and the supporting tissues, as well as for the therapy of related diseases, which agent administered as such, delays or prevents the progression of the disease, or starts the healing process.